Abstract

Motor neurons die selectively in amyotrophic lateral sclerosis (ALS) and during embryonic development. At present, the precise mechanisms responsible for motor neuron death are not known. The proposed experiments will determine whether different motor neuron populations in human and developing rats differentially express molecular subtypes of non-NMDA GluR.
The first aim will test the hypotheses that the expression and localization of specific molecular subtypes of non-NMDA GluR are different in motor neuron populations in human CNS and that the GluR phenotypes of surviving upper and lower motor neurons are changed selectively in spinal cord and selective brain regions in individuals with ALS.
The second aim proposes that subunit switches in the expression of specific GluR in motor neurons occur prior to or during developmental cell death in the rat.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034100-02
Application #
2431274
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Kerza-Kwiatecki, a P
Project Start
1996-09-10
Project End
1999-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Pathology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Martin, Lee J; Wong, Margaret (2017) Enforced DNA repair enzymes rescue neurons from apoptosis induced by target deprivation and axotomy in mouse models of neurodegeneration. Mech Ageing Dev 161:149-162
Chang, Qing; Martin, Lee J (2016) Voltage-gated calcium channels are abnormal in cultured spinal motoneurons in the G93A-SOD1 transgenic mouse model of ALS. Neurobiol Dis 93:78-95
Martin, Lee J; Semenkow, Samantha; Hanaford, Allison et al. (2014) Mitochondrial permeability transition pore regulates Parkinson's disease development in mutant ?-synuclein transgenic mice. Neurobiol Aging 35:1132-52
Martin, Lee J; Fancelli, Daniele; Wong, Margaret et al. (2014) GNX-4728, a novel small molecule drug inhibitor of mitochondrial permeability transition, is therapeutic in a mouse model of amyotrophic lateral sclerosis. Front Cell Neurosci 8:433
Martin, Lee J (2012) Biology of mitochondria in neurodegenerative diseases. Prog Mol Biol Transl Sci 107:355-415
Martin, Lee J; Chang, Qing (2012) Inhibitory synaptic regulation of motoneurons: a new target of disease mechanisms in amyotrophic lateral sclerosis. Mol Neurobiol 45:30-42
Gertz, Barry; Wong, Margaret; Martin, Lee J (2012) Nuclear localization of human SOD1 and mutant SOD1-specific disruption of survival motor neuron protein complex in transgenic amyotrophic lateral sclerosis mice. J Neuropathol Exp Neurol 71:162-77
Martin, Lee J (2011) Mitochondrial pathobiology in ALS. J Bioenerg Biomembr 43:569-79
Northington, Frances J; Chavez-Valdez, Raul; Martin, Lee J (2011) Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol 69:743-58
Chang, Qing; Martin, Lee J (2011) Glycine receptor channels in spinal motoneurons are abnormal in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci 31:2815-27

Showing the most recent 10 out of 74 publications